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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-000072-17 | EudraCT Number |
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| Name | Class |
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| Chugai Pharmaceutical | INDUSTRY |
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This is a randomized, global, multicenter, open-label, Phase 3 clinical study in participants with severe hemophilia A without inhibitors against Factor VIII (FVIII) who are 12 years or older. The study evaluates two prophylactic emicizumab regimens versus no prophylaxis in this population with emphasis on efficacy, safety, and pharmacokinetics.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm C (Control): No Prophylaxis, Then Emicizumab | Active Comparator | Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial. After completing 24 weeks of no prophylaxis (i.e., episodic FVIII treatment) on study, then they were given the opportunity to switch to emicizumab prophylaxis of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| Arm A: Emicizumab 1.5 mg/kg QW | Experimental | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| Arm B: Emicizumab 3 mg/kg Q2W | Experimental | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Emicizumab | Drug | Participants received emicizumab prophylaxis subcutaneously at the specified dose for each arm. After at least 24 weeks on prophylactic emicizumab, individuals who experienced suboptimal bleeding control on emicizumab (according to protocol-defined criteria) had the opportunity to increase their dose to 3 mg/kg weekly. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant had the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg once every 4 weeks [Q4W]) and continue on that dosing regimen until discontinuation from the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Bleeding Rate (ABR) for Treated Bleeds | The number of treated bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a negative binomial (NB) regression model, which accounts for different follow-up times, with the number of bleeds as a function of randomization and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded. | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Bleeding Rate (ABR) for All Bleeds | The number of all bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Santa Monica Oncology Center | Santa Monica | California | 90403 | United States | ||
| Georgetown Uni Medical Center; Lombardi Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35939785 | Derived | Kruse-Jarres R, Peyvandi F, Oldenburg J, Chang T, Chebon S, Doral MY, Croteau SE, Lambert T, Kempton CL, Pipe SW, Ko RH, Trzaskoma B, Dhalluin C, Bienz NS, Niggli M, Lehle M, Paz-Priel I, Young G, Jimenez-Yuste V. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Blood Adv. 2022 Dec 27;6(24):6140-6150. doi: 10.1182/bloodadvances.2022007458. | |
| 35905294 |
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A total of 161 participants were screened; 9 failed screening, and 152 participants, who had previously received either episodic or prophylactic treatment with FVIII agents, were enrolled in this study. Participants in Arms C, A, and B were randomized in a 1:2:2 ratio, respectively; participants in Arm D were enrolled without randomization.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm C (Control): No Prophylaxis, Then Emicizumab | Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial. After completing 24 weeks of no prophylaxis (i.e., episodic FVIII treatment) on study, then they were given the opportunity to switch to emicizumab prophylaxis of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 20, 2019 | Oct 19, 2022 |
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| Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Experimental | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| Factor VIII (FVIII) | Drug | FVIII was allowed to treat bleeds on an episodic basis, per the local prescribing information. Specific dosages of FVIII were not mandated in the study. Breakthrough bleeds were to be treated with the lowest FVIII dose expected to achieve hemostasis, which may have been lower than the participant's prior FVIII dose. To avoid bleeds before adequate emicizumab level is reached, patients in Arm D continued their regular FVIII prophylaxis until the second emicizumab loading dose. Concomitant routine FVIII prophylaxis was not permissible otherwise during the study. |
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| From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
| Annualized Bleeding Rate (ABR) for Treated Joint Bleeds | The number of treated joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A "joint bleed" is defined as a bleed reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint; and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. It is considered a "treated joint bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded. | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
| Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds | The number of treated spontaneous bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded. | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
| Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds | The number of treated target joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A "target joint bleed" is defined as a bleed reported as a joint bleed into a target joint, defined as at least 3 bleeds into the same joint during the last 24 weeks prior to study entry. It is considered a "treated target joint bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded. | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
| Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With Factor VIII (FVIII) Prophylaxis (NISP) | This is an intra-participant comparison of the annualized bleeding rate (ABR) for treated bleeds on study versus pre-study in the NIS population previously treated with FVIII prophylaxis in NIS BH29768. The number of treated bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded. | Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for Dnisp-FVIII Prophylaxis: 30.07 [5.0-45.1] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for Dnisp-Emicizumab Prophylaxis: 33.71 [20.1-48.6] weeks) |
| Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With FVIII Prophylaxis (NISP) | This is an intra-participant comparison of the annualized bleeding rate (ABR) for all bleeds on study versus pre-study in the NIS population previously treated with FVIII prophylaxis in NIS BH29768. The number of all bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the participant's number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. | Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for Dnisp-FVIII Prophylaxis: 30.07 [5.0-45.1] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for Dnisp-Emicizumab Prophylaxis: 33.71 [20.1-48.6] weeks) |
| Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE) | This is an intra-participant comparison of the annualized bleeding rate (ABR) for treated bleeds on study versus pre-study in the NIS population previously treated with episodic FVIII in NIS BH29768. The number of treated bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded. | Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for A+Bnise-FVIII Episodic: 25.71 [15.4-40.9] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for A+Bnise-Emicizumab: 34.71 [24.1-50.6] weeks) |
| Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE) | This is an intra-participant comparison of the annualized bleeding rate (ABR) for all bleeds on study versus pre-study in the NIS population previously treated with episodic FVIII in NIS BH29768. The number of all bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the participant's number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. | Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for A+Bnise-FVIII Episodic: 25.71 [15.4-40.9] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for A+Bnise-Emicizumab: 34.71 [24.1-50.6] weeks) |
| Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Physical Health Subscore for Adult Participants (≥18 Years of Age) in the Randomized Population at Week 25 | The Haem-A-QoL questionnaire has been developed and used in hemophilia A participants, assessing very specific aspects of dealing with hemophilia. The questionnaire consists of items pertaining to 10 domains: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain ranges from 0 to 100 with lower scores reflective of better quality of life. Physical Health domain score is reported (range 0 to 100, with lower scores reflective of better physical health). The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term. | Baseline, Week 25 |
| Haem-A-QoL Questionnaire Total Score for Adult Participants (≥18 Years of Age) in the Randomized Population at Week 25 | The Haem-A-QoL questionnaire has been developed and used in hemophilia A participants, assessing very specific aspects of dealing with hemophilia. The questionnaire consists of items pertaining to 10 domains: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain ranges from 0 to 100 with lower scores reflective of better quality of life. Haem-A-QoL Total Score is the average of all domain scores and it ranges from 0 to 100, with lower scores reflective of better quality of life. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term. | Baseline, Week 25 |
| European Quality of Life 5-Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score in the Randomized Population at Week 25 | EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L VAS. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term. | Baseline, Week 25 |
| EQ-5D-5L Questionnaire Index Utility Score in the Randomized Population at Week 25 | EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L VAS. The EQ-5D-5L health state profile is designed to record the participant's current health state in 5 domains: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. Responses from the five domains are used to calculate a single index utility score on a scale of 0 to 1, with higher scores reflective of better quality of life. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term. | Baseline, Week 25 |
| Hemophilia-Specific Quality of Life - Short Form (Haemo-QoL-SF) Questionnaire Score in Adolescent Participants (12 to 17 Years of Age) in the Randomized Population at Week 25 | The Haemo-QoL-SF contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia and treatment). Items are rated with five respective response options: never, seldom, sometimes, often, and always. Haemo-QoL-SF total score range from 0 to 100, where lower scores reflect better health-related quality of life. | Week 25 |
| Percentage of Participants With at Least One Adverse Event During the First 24 Weeks of the Study, Primary Analysis | The percentage of participants experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Grade ≥3 Adverse Event During the First 24 Weeks of the Study, Primary Analysis | The World Health Organization (WHO) toxicity grading scale will be used for assessing adverse event severity. For adverse events that are not specifically listed in the WHO toxicity grading scale, a grade 3 adverse event is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a grade 4 adverse event is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment During the First 24 Weeks of the Study, Primary Analysis | At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Adverse Event of Changes From Baseline in Vital Signs During the First 24 Weeks of the Study, Primary Analysis | The percentage of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result is reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); results in a medical intervention or a change in concomitant therapy; or is clinically significant in the investigator's judgment. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Adverse Event of Changes From Baseline in Physical Examination Findings During the First 24 Weeks of the Study, Primary Analysis | Post-baseline physical examination abnormalities that were not present at baseline or worsened were reported as adverse events. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Adverse Event of Abnormal Laboratory Values During the First 24 Weeks of the Study, Primary Analysis | The percentage of participants with adverse events of abnormal laboratory values is reported here. An abnormal laboratory value is defined as a laboratory test result outside of the normal range for hematology or serum chemistries. It is reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); results in a medical intervention or a change in concomitant therapy; or is clinically significant in the investigator's judgment. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Local Injection-Site Reaction During the First 24 Weeks of the Study, Primary Analysis | Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an "injection-site reaction" on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a "local injection-site reaction." At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Thromboembolic Event During the First 24 Weeks of the Study, Primary Analysis | At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Thrombotic Microangiopathy During the First 24 Weeks of the Study, Primary Analysis | At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Percentage of Participants With at Least One Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction During the First 24 Weeks of the Study, Primary Analysis | At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
| Safety Summary of the Percentage of Emicizumab-Treated Participants With at Least One Adverse Event During the Study | Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms "severe" and "serious" are not synonymous; severity and seriousness were independently assessed for each AE. For participants whose emicizumab dose was up-titrated and those who opted for a change in dosing regimen (after implementation of protocol v4), only AEs that occurred before either one of those events are included. Hypersens.= hypersensitivity; Mod. = modification | From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks) |
| Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants | The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded. | From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks) |
| Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants | The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded. | From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks) |
| Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants | The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded. | From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks) |
| Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
| Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
| Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
| Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
| Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
| Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
| Percentage of Participants With Anti-Emicizumab Antibodies at Any Time Post-Baseline During the Study | A validated enzyme-linked immunosorbent assay (ELISA) method was used to analyze the levels of anti-drug antibodies (ADAs) against emicizumab in plasma. A sample was considered positive for anti-emicizumab antibodies if the test result reached or exceeded a pre-determined threshold. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. | From Baseline to discontinuation from study (median [min-max] observation period for all emicizumab participants: 262.3 [14.4-288.3] weeks) |
| Percentage of Participants With De Novo Development of Factor VIII (FVIII) Inhibitors | Levels of anti-FVIII antibodies (inhibitors) were analyzed using a validated FVIII activity assay. A participant was considered to have developed de novo FVIII inhibitors if the inhibitor levels detected in a post-baseline sample reached or exceeded a pre-determined threshold. | From Baseline to discontinuation from study (median [min-max] observation period for all emicizumab participants: 262.3 [14.4-288.3] weeks) |
| Trough Plasma Concentration (Ctrough) of Emicizumab | Trough plasma concentrations of emicizumab were analyzed using a validated Enzyme Linked Immunosorbent Assay (ELISA). The lower limit of quantification (LLOQ) was 100 nanograms per milliliter (ng/mL). Because participants in Arm C (Control) switched from no prophylaxis to start receiving emicizumab prophylaxis after Week 24, the timepoints for Arm C (Emi) are expressed relative to first emicizumab dose. | Predose at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, 217, 229, 241, 253, 265, and 277 |
| Washington D.C. |
| District of Columbia |
| 20007 |
| United States |
| University of Florida | Gainesville | Florida | 32607 | United States |
| Winship Cancer Institute | Atlanta | Georgia | 30322 | United States |
| Dana-Farber Cancer Institute; Brigham and Women's Cancer Center | Boston | Massachusetts | 02115 | United States |
| Children's Hospital of Michigan; Pediatrics | Detroit | Michigan | 48201 | United States |
| Cornell Univ Medical College; Hematology-Oncolog | New York | New York | 10021 | United States |
| Bloodworks Northwest (formerly Puget Sound Blood Center); Hemophilia | Seattle | Washington | 98104 | United States |
| Royal Adelaide Hospital | Adelaide | South Australia | 5000 | Australia |
| The Alfred Hospital, Melbourne; Thrombosis and Haemostasis Unit | Melbourne | Victoria | 3004 | Australia |
| The Perth Blood Institute | Nedlands | Western Australia | 6009 | Australia |
| ICIC | San José | 1000 | Costa Rica |
| Hopital Cardio-vasculaire Louis Pradel; Hemostase clinique | Bron | 69677 | France |
| CH de Bicetre; Centre de Traitement d' Hemophilie | Le Kremlin-Bicêtre | 94275 | France |
| Groupe Hospitalier Necker Enfants Malades | Paris | 75015 | France |
| Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin | Bonn | 53127 | Germany |
| St James's Hospital | Dublin | 8 | Ireland |
| IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi" | Milan | Lombardy | 20122 | Italy |
| AOU Careggi; SOD Malattie Emorragiche | Florence | Tuscany | 50134 | Italy |
| Nagoya University Hospital | Aichi | 466-8560 | Japan |
| St. Marianna University Hospital | Kanagawa | 216-8511 | Japan |
| Sendai Medical Center | Miyagi | 983-8520 | Japan |
| Nara Medical University Hospital | Nara | 634-8522 | Japan |
| NHO Osaka National Hospital | Osaka | 540-0006 | Japan |
| Tokyo Medical University Hospital | Tokyo | 160-0023 | Japan |
| Ogikubo Hospital | Tokyo | 167-0035 | Japan |
| Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii | Gdansk | 80-952 | Poland |
| SPSK Nr1 Klinika Hematoo&Transpl.Szpiku | Lublin | 20-081 | Poland |
| ALVAMED Lekarskie Gabinety Specjalistyczne | Poznan | 60-549 | Poland |
| Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych | Warsaw | 02-776 | Poland |
| Charlotte Maxeke Johannesburg Hospital; Haemophilia Comprehensive Care Center | Johannesburg | 2193 | South Africa |
| Severance Hospital | Seoul | 03722 | South Korea |
| Hospital Universitario la Paz; Servicio de Hematologia | Madrid | 28046 | Spain |
| Hospital Universitario Virgen del Rocio; Servicio de Hematologia | Seville | 41013 | Spain |
| Changhua Christian Hospital | Chang-hua | 500 | Taiwan |
| Taichung Veterans General Hospital | Taichung | 40705 | Taiwan |
| Taipei Medical University Hospital | Taipei | 110 | Taiwan |
| Cardiff and Vale NHS Trust | Cardiff | CF14 4XW | United Kingdom |
| Royal Free Hospital; Haemophilia Centre | London | NW3 2QG | United Kingdom |
| Derived |
| Kiialainen A, Niggli M, Kempton CL, Castaman G, Chang T, Paz-Priel I, Adamkewicz JI, Levy GG. Effect of emicizumab prophylaxis on bone and joint health markers in people with haemophilia A without factor VIII inhibitors in the HAVEN 3 study. Haemophilia. 2022 Nov;28(6):1033-1043. doi: 10.1111/hae.14642. Epub 2022 Jul 29. |
| 30157389 | Derived | Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, Schmitt C, Jimenez-Yuste V, Kempton C, Dhalluin C, Callaghan MU, Bujan W, Shima M, Adamkewicz JI, Asikanius E, Levy GG, Kruse-Jarres R. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018 Aug 30;379(9):811-822. doi: 10.1056/NEJMoa1803550. |
| FG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| FG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| FG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| Completed First 24 Weeks of Treatment |
|
| Emicizumab Dose Was Up-Titrated |
|
| Opted to Change Emicizumab Dosing Regimen | Upon Implementation of Protocol Version 4 |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm C (Control): No Prophylaxis, Then Emicizumab | Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial. After completing 24 weeks of no prophylaxis (i.e., episodic FVIII treatment) on study, then they were given the opportunity to switch to emicizumab prophylaxis of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| BG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| BG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| BG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Number of Participants with <9 or ≥9 Bleeds in the Last 24 Weeks Prior to Study Entry | Count of Participants | Participants |
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| Number of Target Joints in the Last 24 Weeks Prior to Study Entry | A target joint was defined as at least 3 bleeds into the same joint over the last 24 weeks prior to study entry. | Mean | Standard Deviation | target joints |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Annualized Bleeding Rate (ABR) for Treated Bleeds | The number of treated bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a negative binomial (NB) regression model, which accounts for different follow-up times, with the number of bleeds as a function of randomization and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded. | All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study. | Posted | Number | 95% Confidence Interval | treated bleed rate per year | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
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| Secondary | Annualized Bleeding Rate (ABR) for All Bleeds | The number of all bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. | All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study. | Posted | Number | 95% Confidence Interval | all bleed rate per year | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
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| Secondary | Annualized Bleeding Rate (ABR) for Treated Joint Bleeds | The number of treated joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A "joint bleed" is defined as a bleed reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint; and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. It is considered a "treated joint bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded. | All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study. | Posted | Number | 95% Confidence Interval | treated joint bleed rate per year | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
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| Secondary | Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds | The number of treated spontaneous bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded. | All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study. | Posted | Number | 95% Confidence Interval | treated spontaneous bleed rate per year | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
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| Secondary | Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds | The number of treated target joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A "target joint bleed" is defined as a bleed reported as a joint bleed into a target joint, defined as at least 3 bleeds into the same joint during the last 24 weeks prior to study entry. It is considered a "treated target joint bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded. | All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study. | Posted | Number | 95% Confidence Interval | treated target joint bleed rate per year | From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks) |
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| Secondary | Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With Factor VIII (FVIII) Prophylaxis (NISP) | This is an intra-participant comparison of the annualized bleeding rate (ABR) for treated bleeds on study versus pre-study in the NIS population previously treated with FVIII prophylaxis in NIS BH29768. The number of treated bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded. | Intra-participant comparison in the NIS population previously treated with FVIII prophylaxis (NISP), which includes all participants who had received FVIII prophylaxis in NIS BH29768 prior to study entry in Arm D. | Posted | Number | 95% Confidence Interval | treated bleed rate per year | Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for Dnisp-FVIII Prophylaxis: 30.07 [5.0-45.1] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for Dnisp-Emicizumab Prophylaxis: 33.71 [20.1-48.6] weeks) |
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| Secondary | Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With FVIII Prophylaxis (NISP) | This is an intra-participant comparison of the annualized bleeding rate (ABR) for all bleeds on study versus pre-study in the NIS population previously treated with FVIII prophylaxis in NIS BH29768. The number of all bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the participant's number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. | Intra-participant comparison in the NIS population previously treated with FVIII prophylaxis (NISP), which includes all participants who had received FVIII prophylaxis in NIS BH29768 prior to study entry in Arm D. | Posted | Number | 95% Confidence Interval | all bleed rate per year | Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for Dnisp-FVIII Prophylaxis: 30.07 [5.0-45.1] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for Dnisp-Emicizumab Prophylaxis: 33.71 [20.1-48.6] weeks) |
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| Secondary | Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE) | This is an intra-participant comparison of the annualized bleeding rate (ABR) for treated bleeds on study versus pre-study in the NIS population previously treated with episodic FVIII in NIS BH29768. The number of treated bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded. | Intra-participant comparison in the NIS population previously treated with episodic FVIII (NISE), which includes all participants who had received episodic FVIII in NIS BH29768 prior to study entry in Arms A and B (pooled data). | Posted | Number | 95% Confidence Interval | treated bleed rate per year | Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for A+Bnise-FVIII Episodic: 25.71 [15.4-40.9] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for A+Bnise-Emicizumab: 34.71 [24.1-50.6] weeks) |
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| Secondary | Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE) | This is an intra-participant comparison of the annualized bleeding rate (ABR) for all bleeds on study versus pre-study in the NIS population previously treated with episodic FVIII in NIS BH29768. The number of all bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the participant's number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. | Intra-participant comparison in the NIS population previously treated with episodic FVIII (NISE), which includes all participants who had received episodic FVIII in NIS BH29768 prior to study entry in Arms A and B (pooled data). | Posted | Number | 95% Confidence Interval | all bleed rate per year | Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for A+Bnise-FVIII Episodic: 25.71 [15.4-40.9] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for A+Bnise-Emicizumab: 34.71 [24.1-50.6] weeks) |
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| Secondary | Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Physical Health Subscore for Adult Participants (≥18 Years of Age) in the Randomized Population at Week 25 | The Haem-A-QoL questionnaire has been developed and used in hemophilia A participants, assessing very specific aspects of dealing with hemophilia. The questionnaire consists of items pertaining to 10 domains: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain ranges from 0 to 100 with lower scores reflective of better quality of life. Physical Health domain score is reported (range 0 to 100, with lower scores reflective of better physical health). The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term. | Adult participants randomized to Arms A, B, and C. The number analyzed represents participants who provided responses at Baseline and Week 25. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 25 |
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| Secondary | Haem-A-QoL Questionnaire Total Score for Adult Participants (≥18 Years of Age) in the Randomized Population at Week 25 | The Haem-A-QoL questionnaire has been developed and used in hemophilia A participants, assessing very specific aspects of dealing with hemophilia. The questionnaire consists of items pertaining to 10 domains: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain ranges from 0 to 100 with lower scores reflective of better quality of life. Haem-A-QoL Total Score is the average of all domain scores and it ranges from 0 to 100, with lower scores reflective of better quality of life. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term. | Adult participants randomized to Arms A, B, and C. The number analyzed represents participants who provided responses at Baseline and Week 25. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 25 |
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| Secondary | European Quality of Life 5-Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score in the Randomized Population at Week 25 | EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L VAS. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term. | Participants randomized to Arms A, B, and C. The number analyzed represents participants who provided responses at Baseline and Week 25. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 25 |
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| Secondary | EQ-5D-5L Questionnaire Index Utility Score in the Randomized Population at Week 25 | EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L VAS. The EQ-5D-5L health state profile is designed to record the participant's current health state in 5 domains: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. Responses from the five domains are used to calculate a single index utility score on a scale of 0 to 1, with higher scores reflective of better quality of life. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term. | Participants randomized to Arms A, B, and C. The number analyzed represents participants who provided responses at Baseline and Week 25. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 25 |
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| Secondary | Hemophilia-Specific Quality of Life - Short Form (Haemo-QoL-SF) Questionnaire Score in Adolescent Participants (12 to 17 Years of Age) in the Randomized Population at Week 25 | The Haemo-QoL-SF contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia and treatment). Items are rated with five respective response options: never, seldom, sometimes, often, and always. Haemo-QoL-SF total score range from 0 to 100, where lower scores reflect better health-related quality of life. | The pre-specified efficacy objective was the comparison of Haemo-QoL-SF scores at Week 25 in adolescents who were previously on episodic treatment (i.e., randomized to Arms A, B, or C). Because there was a total of just one adolescent randomized to this study (in Arm C), statistical analyses could not be performed and no data is reported. | Posted | Week 25 |
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| Secondary | Percentage of Participants With at Least One Adverse Event During the First 24 Weeks of the Study, Primary Analysis | The percentage of participants experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Grade ≥3 Adverse Event During the First 24 Weeks of the Study, Primary Analysis | The World Health Organization (WHO) toxicity grading scale will be used for assessing adverse event severity. For adverse events that are not specifically listed in the WHO toxicity grading scale, a grade 3 adverse event is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a grade 4 adverse event is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment During the First 24 Weeks of the Study, Primary Analysis | At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Adverse Event of Changes From Baseline in Vital Signs During the First 24 Weeks of the Study, Primary Analysis | The percentage of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result is reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); results in a medical intervention or a change in concomitant therapy; or is clinically significant in the investigator's judgment. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Adverse Event of Changes From Baseline in Physical Examination Findings During the First 24 Weeks of the Study, Primary Analysis | Post-baseline physical examination abnormalities that were not present at baseline or worsened were reported as adverse events. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Adverse Event of Abnormal Laboratory Values During the First 24 Weeks of the Study, Primary Analysis | The percentage of participants with adverse events of abnormal laboratory values is reported here. An abnormal laboratory value is defined as a laboratory test result outside of the normal range for hematology or serum chemistries. It is reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); results in a medical intervention or a change in concomitant therapy; or is clinically significant in the investigator's judgment. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Local Injection-Site Reaction During the First 24 Weeks of the Study, Primary Analysis | Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an "injection-site reaction" on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a "local injection-site reaction." At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Thromboembolic Event During the First 24 Weeks of the Study, Primary Analysis | At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Thrombotic Microangiopathy During the First 24 Weeks of the Study, Primary Analysis | At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Percentage of Participants With at Least One Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction During the First 24 Weeks of the Study, Primary Analysis | At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of at least 24 weeks. | All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C (Control) who started the no prophylaxis study period. Participants in Arm C (Emi) are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis). | Posted | Number | percentage of participants | From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks) |
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| Secondary | Safety Summary of the Percentage of Emicizumab-Treated Participants With at Least One Adverse Event During the Study | Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms "severe" and "serious" are not synonymous; severity and seriousness were independently assessed for each AE. For participants whose emicizumab dose was up-titrated and those who opted for a change in dosing regimen (after implementation of protocol v4), only AEs that occurred before either one of those events are included. Hypersens.= hypersensitivity; Mod. = modification | All Emicizumab Participants, which includes all participants who received emicizumab on the study. For Arm C (Emi), it only includes participants who crossed over to receive prophylactic treatment with emicizumab after first completing 24 weeks of no prophylaxis on study (1 participant was excluded because they were lost to follow-up before Week 24 and did not receive emicizumab). | Posted | Number | percentage of participants | From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks) |
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| Secondary | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants | The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. For Arm C, it only includes participants who crossed over to receive prophylactic treatment with emicizumab after first completing 24 weeks of no prophylaxis on study. | Posted | Number | 95% Confidence Interval | bleeds per year | From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks) |
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| Secondary | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants | The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. For Arm C, it only includes participants who crossed over to receive prophylactic treatment with emicizumab after first completing 24 weeks of no prophylaxis on study. | Posted | Mean | 95% Confidence Interval | bleeds per year | From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks) |
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| Secondary | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants | The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. For Arm C, it only includes participants who crossed over to receive prophylactic treatment with emicizumab after first completing 24 weeks of no prophylaxis on study. | Posted | Median | Inter-Quartile Range | bleeds per year | From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks) |
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| Secondary | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. The number analyzed includes participants with available data over each interval. | Posted | Mean | 95% Confidence Interval | Treated bleeds per year | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
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| Secondary | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. The number analyzed includes participants with available data over each interval. | Posted | Median | Inter-Quartile Range | Treated bleeds per year | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
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| Secondary | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. The number analyzed includes participants with available data over each interval. | Posted | Mean | 95% Confidence Interval | All bleeds per year | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
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| Secondary | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. The number analyzed includes participants with available data over each interval. | Posted | Median | Inter-Quartile Range | All bleeds per year | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
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| Secondary | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. The number analyzed includes participants with available data over each interval. | Posted | Mean | 95% Confidence Interval | Treated spontaneous bleeds per year | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
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| Secondary | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants | The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v4), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen. | All Emicizumab Participants, which includes all participants who received emicizumab on the study. The number analyzed includes participants with available data over each interval. | Posted | Median | Inter-Quartile Range | Treated spontaneous bleeds per year | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks |
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| Secondary | Percentage of Participants With Anti-Emicizumab Antibodies at Any Time Post-Baseline During the Study | A validated enzyme-linked immunosorbent assay (ELISA) method was used to analyze the levels of anti-drug antibodies (ADAs) against emicizumab in plasma. A sample was considered positive for anti-emicizumab antibodies if the test result reached or exceeded a pre-determined threshold. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. | The All Emicizumab Population includes all participants in Arms A, B, C (Emi), and D treated with emicizumab; 1 was excluded from Arm C (Emi) (lost to follow-up before Week 24 and had not switched to emicizumab). | Posted | Number | percentage of participants | From Baseline to discontinuation from study (median [min-max] observation period for all emicizumab participants: 262.3 [14.4-288.3] weeks) |
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| Secondary | Percentage of Participants With De Novo Development of Factor VIII (FVIII) Inhibitors | Levels of anti-FVIII antibodies (inhibitors) were analyzed using a validated FVIII activity assay. A participant was considered to have developed de novo FVIII inhibitors if the inhibitor levels detected in a post-baseline sample reached or exceeded a pre-determined threshold. | The All Emicizumab Population includes all participants in Arms A, B, C (Emi), and D treated with emicizumab; 1 was excluded from Arm C (Emi) (lost to follow-up before Week 24 and had not switched to emicizumab). | Posted | Number | percentage of participants | From Baseline to discontinuation from study (median [min-max] observation period for all emicizumab participants: 262.3 [14.4-288.3] weeks) |
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| Secondary | Trough Plasma Concentration (Ctrough) of Emicizumab | Trough plasma concentrations of emicizumab were analyzed using a validated Enzyme Linked Immunosorbent Assay (ELISA). The lower limit of quantification (LLOQ) was 100 nanograms per milliliter (ng/mL). Because participants in Arm C (Control) switched from no prophylaxis to start receiving emicizumab prophylaxis after Week 24, the timepoints for Arm C (Emi) are expressed relative to first emicizumab dose. | The Pharmacokinetics (PK) Population includes all participants in Arms A, B, C (Emi), and D treated with emicizumab who had at least one post-dose emicizumab concentration result; 1 was excluded from Arm C (Emi) (lost to follow-up before Week 24 and had not switched to emicizumab). Number analyzed represents participants per study arm with available samples at each specified timepoint. | Posted | Mean | Standard Deviation | micrograms per milliliter (μg/mL) | Predose at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, 217, 229, 241, 253, 265, and 277 |
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Total observation time for all participants: From enrollment until study completion (median [min-max] 262.3 [14.4-288.3] weeks); Arm C (Control): From enrollment to 24 weeks on no prophylaxis (median [min-max]: 24.00 [14.4-25.0] weeks)
All adverse events (AEs) in emicizumab-treated subjects are reported, including after dose up-titration or change of dosing regimen. AEs in Arm C are reported in 2 groups: Arm C (Control) for the first 24 weeks on no prophylaxis; Arm C (Emi) for those who switched after 24 weeks to receive emicizumab prophylaxis.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm C (Control): No Prophylaxis | Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis. The results for this control arm represent data collected during the first 24 weeks on study while receiving their usual care of episodic treatment with FVIII. | 0 | 18 | 1 | 18 | 5 | 18 |
| EG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. | 0 | 36 | 10 | 36 | 35 | 36 |
| EG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. | 0 | 35 | 8 | 35 | 33 | 35 |
| EG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis during the entire study after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC Q2W. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. | 0 | 17 | 1 | 17 | 15 | 17 |
| EG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. | 0 | 63 | 16 | 63 | 61 | 63 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ACUTE CORONARY SYNDROME | Cardiac disorders | MedDRA version 25.0 | Systematic Assessment |
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| ACUTE MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA version 25.0 | Systematic Assessment |
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| ARRHYTHMIA | Cardiac disorders | MedDRA version 25.0 | Systematic Assessment |
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| ATRIAL FLUTTER | Cardiac disorders | MedDRA version 25.0 | Systematic Assessment |
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| HYPERPARATHYROIDISM | Endocrine disorders | MedDRA version 25.0 | Systematic Assessment |
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| ANAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| FISTULA OF SMALL INTESTINE | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| GASTRIC HAEMORRHAGE | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| HAEMATEMESIS | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| HAEMATOCHEZIA | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| MALLORY-WEISS SYNDROME | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| MELAENA | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| PANCREATITIS | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| RECTAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| RETROPERITONEAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| SPLENIC ARTERY ANEURYSM | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| UPPER GASTROINTESTINAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| ASTHENIA | General disorders | MedDRA version 25.0 | Systematic Assessment |
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| ABSCESS LIMB | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| APPENDICITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| ARTHRITIS BACTERIAL | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| GINGIVAL ABSCESS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| PYELONEPHRITIS ACUTE | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| SUBPERIOSTEAL ABSCESS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| TONSILLITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| WOUND INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
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| DURAL TEAR | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| FEMORAL NECK FRACTURE | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| FEMUR FRACTURE | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| MUSCLE RUPTURE | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| MUSCLE STRAIN | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| POISONING | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| POST PROCEDURAL HAEMATOMA | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| ROAD TRAFFIC ACCIDENT | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| TENDON RUPTURE | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
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| DIABETES MELLITUS | Metabolism and nutrition disorders | MedDRA version 25.0 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
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| GROIN PAIN | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
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| OSTEOARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
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| RHABDOMYOLYSIS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
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| SYNOVITIS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
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| BONE GIANT CELL TUMOUR BENIGN | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Systematic Assessment |
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| PAPILLARY THYROID CANCER | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Systematic Assessment |
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| PARATHYROID TUMOUR BENIGN | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Systematic Assessment |
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| SALIVARY GLAND NEOPLASM | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Systematic Assessment |
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| CEREBRAL HAEMORRHAGE | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
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| CEREBROSPINAL FLUID LEAKAGE | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
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| PUTAMEN HAEMORRHAGE | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
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| SEIZURE | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
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| DEVICE LOOSENING | Product Issues | MedDRA version 25.0 | Systematic Assessment |
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| SUICIDAL IDEATION | Psychiatric disorders | MedDRA version 25.0 | Systematic Assessment |
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| HAEMATURIA | Renal and urinary disorders | MedDRA version 25.0 | Systematic Assessment |
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| NEPHROLITHIASIS | Renal and urinary disorders | MedDRA version 25.0 | Systematic Assessment |
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| RENAL HAEMATOMA | Renal and urinary disorders | MedDRA version 25.0 | Systematic Assessment |
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| URETEROLITHIASIS | Renal and urinary disorders | MedDRA version 25.0 | Systematic Assessment |
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| EPISTAXIS | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| HAEMATOMA | Vascular disorders | MedDRA version 25.0 | Systematic Assessment |
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| HAEMORRHAGE | Vascular disorders | MedDRA version 25.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HYDROCELE | Congenital, familial and genetic disorders | MedDRA version 25.0 | Systematic Assessment |
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| TINNITUS | Ear and labyrinth disorders | MedDRA version 25.0 | Systematic Assessment |
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| HYPOTHYROIDISM | Endocrine disorders | MedDRA version 25.0 | Systematic Assessment |
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| CATARACT | Eye disorders | MedDRA version 25.0 | Systematic Assessment |
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| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| CONSTIPATION | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| DENTAL CARIES | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| DIARRHOEA | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| DYSPEPSIA | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| GASTRITIS | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| GASTROOESOPHAGEAL REFLUX DISEASE | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| LARGE INTESTINE POLYP | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
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| ASTHENIA | General disorders | MedDRA version 25.0 | Systematic Assessment |
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| INFLUENZA LIKE ILLNESS | General disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| INJECTION SITE REACTION | General disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| PAIN | General disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| PYREXIA | General disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| DRUG HYPERSENSITIVITY | Immune system disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| HYPERSENSITIVITY | Immune system disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| SEASONAL ALLERGY | Immune system disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| BACTERIAL INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| BODY TINEA | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| BRONCHITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| CONJUNCTIVITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| CORONAVIRUS INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| DIARRHOEA INFECTIOUS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| EAR INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| GASTRIC INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| GASTROENTERITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| INFLUENZA | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| LOCALISED INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| LOWER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| NASOPHARYNGITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| PERIODONTITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| PHARYNGITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| RHINITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| SINUSITIS | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| ARTHROPOD BITE | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| BACK INJURY | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| BITE | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| CONTUSION | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| FALL | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| JOINT INJURY | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| LIGAMENT INJURY | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| LIGAMENT SPRAIN | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| LIMB INJURY | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| MUSCLE STRAIN | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| ROAD TRAFFIC ACCIDENT | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| SKIN LACERATION | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| TONGUE INJURY | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| TOOTH FRACTURE | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA version 25.0 | Systematic Assessment |
| |
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA version 25.0 | Systematic Assessment |
| |
| BLOOD CREATINE PHOSPHOKINASE INCREASED | Investigations | MedDRA version 25.0 | Systematic Assessment |
| |
| BLOOD CREATININE INCREASED | Investigations | MedDRA version 25.0 | Systematic Assessment |
| |
| BLOOD PRESSURE DIASTOLIC INCREASED | Investigations | MedDRA version 25.0 | Systematic Assessment |
| |
| HYPERCHOLESTEROLAEMIA | Metabolism and nutrition disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| HYPERURICAEMIA | Metabolism and nutrition disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| ARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| GROIN PAIN | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| HAEMOPHILIC ARTHROPATHY | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| JOINT SWELLING | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| MUSCLE CONTRACTURE | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| MUSCULOSKELETAL STIFFNESS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| SYNOVITIS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| PAPILLOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Systematic Assessment |
| |
| DIZZINESS | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| HEADACHE | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| PARAESTHESIA | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| SCIATICA | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| ANXIETY | Psychiatric disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| DEPRESSION | Psychiatric disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| INSOMNIA | Psychiatric disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| SLEEP DISORDER | Psychiatric disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| NEPHROLITHIASIS | Renal and urinary disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| ERECTILE DYSFUNCTION | Reproductive system and breast disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| NASAL CONGESTION | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| OROPHARYNGEAL PAIN | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| ALOPECIA | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| ECZEMA | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| RASH | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| RASH MACULO-PAPULAR | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| HAEMATOMA | Vascular disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| ABSCESS LIMB | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
| |
| SKIN ABRASION | Injury, poisoning and procedural complications | MedDRA version 25.0 | Systematic Assessment |
| |
| TENDONITIS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| TENOSYNOVITIS | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
| |
| HYPERTENSION | Vascular disorders | MedDRA version 25.0 | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 20, 2017 | Sep 14, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| C000608208 | emicizumab |
| D005169 | Factor VIII |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011498 | Protein Precursors |
| D001685 | Biological Factors |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Greater Than or Equal To (≥) 9 Bleeds |
|
| H0 (null hypothesis): ABR Ratio for Arm B versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm B versus Arm C ≠ 1. | Stratified Wald test | <0.0001 | Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value was obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis). | ABR Ratio | 0.03 | 2-Sided | 95 | 0.017 | 0.066 | Arm B is the numerator and Arm C is the denominator for this ABR Ratio. | Superiority |
| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
|
| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
|
| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
|
| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
|
This arm includes historical data from participants in the non-interventional study (NIS) BH29768 who had received FVIII prophylaxis and were followed for a minimum of 24 weeks on the NIS prior to enrollment in Arm D of this study.
| OG001 | Dnisp: Emicizumab Prophylaxis (Pre-Study FVIII Prophylaxis) | This arm includes data from the same participants who had received FVIII prophylaxis in NIS BH29768 prior to study entry and then enrolled in Arm D of this study to receive emicizumab prophylaxis at a dose of 3 mg/kg once per week (QW) subcutaneously (SC) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW until the end of study. The data reported was collected only during emicizumab prophylaxis treatment. |
|
|
|
| OG001 | Dnisp: Emicizumab Prophylaxis (Pre-Study FVIII Prophylaxis) | This arm includes data from the same participants who had received FVIII prophylaxis in NIS BH29768 prior to study entry and then enrolled in Arm D of this study to receive emicizumab prophylaxis at a dose of 3 mg/kg once per week (QW) subcutaneously (SC) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW until the end of study. The data reported was collected only during emicizumab prophylaxis treatment. |
|
|
|
| OG001 | A+Bnise: Emicizumab Prophylaxis (Pre-study Episodic FVIII) | This arm includes data from the same participants who had received episodic FVIII treatment in NIS BH29768 prior to study entry and then were randomized to Arms A or B of this study to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of either 1.5 mg/kg emicizumab SC QW (Arm A) or 3 mg/kg emicizumab SC Q2W (Arm B). A pooled analysis, as opposed to two separate analyses, was performed due to the small number of NIS episodic patients (NISE) randomized to either Arm A or B. The data reported was collected only during emicizumab prophylaxis treatment. |
|
|
|
| OG001 | A+Bnise: Emicizumab Prophylaxis (Pre-study Episodic FVIII) | This arm includes data from the same participants who had received episodic FVIII treatment in NIS BH29768 prior to study entry and then were randomized to Arms A or B of this study to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of either 1.5 mg/kg emicizumab SC QW (Arm A) or 3 mg/kg emicizumab SC Q2W (Arm B). A pooled analysis, as opposed to two separate analyses, was performed due to the small number of NIS episodic patients (NISE) randomized to either Arm A or B. The data reported was collected only during emicizumab prophylaxis treatment. |
|
|
|
| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
|
| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
|
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study.
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
|
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
|
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study.
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| Arm A: Emicizumab 1.5 mg/kg QW |
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| OG001 | Arm A: Emicizumab 1.5 mg/kg QW | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
|
|
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study.
| OG002 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis up to PCD) | This arm includes all participants from Arm C who had switched to emicizumab prophylaxis up to the primary completion date (PCD; i.e., analysis cutoff) after having completed 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment up to the PCD. Emicizumab was administered at a loading dose of 3 mg/kg SC once per week (QW) for the first 4 weeks, followed by maintenance dosing of 3 mg/kg emcizumab SC Q2W. |
| OG004 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
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| OG001 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis) | This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg once every 2 weeks SC. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG004 | All Emicizumab Participants | This analysis set included all participants who received emicizumab on the study. For Arm C, it only includes all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. |
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Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG001 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis) | This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg once every 2 weeks SC. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG004 | All Emicizumab Participants | This analysis set included all participants who received emicizumab on the study. For Arm C, it only includes all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. |
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Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG001 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis) | This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg once every 2 weeks SC. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG004 | All Emicizumab Participants | This analysis set included all participants who received emicizumab on the study. For Arm C, it only includes all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. |
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|
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG001 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis) | This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg once every 2 weeks SC. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG004 | All Emicizumab Participants | This analysis set included all participants who received emicizumab on the study. For Arm C, it only includes all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. |
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| OG001 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis) | This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg once every 2 weeks SC. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG004 | All Emicizumab Participants | This analysis set included all participants who received emicizumab on the study. For Arm C, it only includes all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. |
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Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study.
| OG002 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis) | This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg once every 2 weeks SC. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG004 | All Emicizumab Participants | This analysis set included all participants who received emicizumab on the study. For Arm C, it only includes all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. |
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| OG001 | Arm B: Emicizumab 3 mg/kg Q2W | Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG002 | Arm C (Emi): Emicizumab 3 mg/kg Q2W (Switch From No Prophylaxis) | This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing 24 weeks on No Prophylaxis. The data reported was collected only during emicizumab prophylaxis treatment. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg once every 2 weeks SC. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG003 | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study. |
| OG004 | Arms A and D: Emicizumab 1.5 mg/kg QW | This analysis set is a combination of all emicizumab-treated participants from Arms A and D who received the same emicizumab prophylaxis dosing regimen at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by 1.5 mg/kg emicizumab SC QW until discontinuation from the study. |
| OG005 | Arms B and C (Emi): Emicizumab 3 mg/kg Q2W | This analysis set is a combination of all emicizumab-treated participants from Arms B and C (Emi) who received the same emicizumab prophylaxis dosing regimen at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by 3 mg/kg emicizumab SC once every 2 weeks (Q2W) until discontinuation from the study. |
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